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Establishment of novel biomarker for osteoporosis focusing on adrenal-derived metabolites

Research Project

Project/Area Number 20K16525
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionKyushu University

Principal Investigator

Yokomoto-Umakoshi Maki  九州大学, 医学研究院, 特別研究員(RPD) (20789672)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords副腎 / 骨粗鬆症 / ステロイド / ステロイドホルモン / 副腎由来ホルモン / ステロイドミクス / メタボローム / 骨質
Outline of Research at the Start

骨粗鬆症の標準的診断法は骨密度検査であるが、骨折の約50%は骨密度では診断ができず、有用な診断法の確立が課題である。副腎ホルモンは骨強度に影響するが、副腎ホルモン過剰を伴う副腎腫瘍は骨量正常でも高率に骨折をきたす。従来、副腎ホルモンは最終産物により評価するが、予備検討により副腎由来代謝産物を包括的に評価する意義を見出した。副腎由来代謝産物の多様性は普遍的に認めるため、副腎腫瘍をモデルに得られた結果を一般化できると考えた。本研究では、副腎腫瘍を対象として血漿メタボロミクスを行い、骨関連指標と副腎由来代謝産物との関連を解析する。原発性骨粗鬆症で検証し、骨粗鬆症診断バイオマーカーを確立する。

Outline of Final Research Achievements

We found an association of primary aldosteronism and pheochromocytoma with osteoporosis. We also demonstrated the protective effects of adrenal androgens in an Mendelian randomization study, suggesting effects of adrenal-derived hormones on bone metabolism under physiological conditions. Comprehensive steroidomics analysis was performed to investigate the involvement of adrenal-derived steroid metabolites in osteoporosis in Cushing's syndrome. We found that adrenal tumors produce glucocorticoid and mineralocorticoid metabolites, which are associated with bone loss, and that glucocorticoid excess atrophies the adrenal glands and suppresses adrenal androgen production, which is associated with bone quality deterioration.

Academic Significance and Societal Importance of the Research Achievements

主要な内分泌臓器である副腎は、内外のストレスに応答してホルモンを分泌し、生体の恒常性を維持している。副腎は3層構造を呈する皮質と髄質より構成さ れ、皮質では層特異的にステロイドホルモン(ミネラルコルチコイド、グルココルチコイド、副腎アンドロゲン)が産生され、髄質ではカテコールアミンが産生される。ホルモン過剰状態では、ストレス応答性が破綻し、様々な加齢性疾患を引き起こす。コルチゾールの過剰はステロイド骨粗鬆症を引き起こすことはよく 知られているが、その他のホルモンの骨代謝への影響は明らかではなかった。本研究により、多様な副腎由来代謝産物が協調して骨粗鬆症の進展に影響していることが明らかになった。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (2 results) (of which Invited: 2 results)

  • [Journal Article] Coexistence of bone and vascular disturbances in patients with endogenous glucocorticoid excess2022

    • Author(s)
      Yano Chieko、Yokomoto-Umakoshi Maki、Fujita Masamichi、Umakoshi Hironobu、Yano Seiichi、Iwahashi Norifusa、Katsuhara Shunsuke、Kaneko Hiroki、Ogata Masatoshi、Fukumoto Tazuru、Terada Eriko、Matsuda Yayoi、Sakamoto Ryuichi、Ogawa Yoshihiro
    • Journal Title

      Bone Reports

      Volume: 17 Pages: 101610-101610

    • DOI

      10.1016/j.bonr.2022.101610

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of Cortisol on Reduction in Muscle Strength and Mass: A Mendelian Randomization Study2021

    • Author(s)
      Katsuhara Shunsuke、Yokomoto-Umakoshi Maki、Umakoshi Hironobu、Matsuda Yayoi、Iwahashi Norifusa、Kaneko Hiroki、Ogata Masatoshi、Fukumoto Tazuru、Terada Eriko、Sakamoto Ryuichi、Ogawa Yoshihiro
    • Journal Title

      The Journal of Clinical Endocrinology Metabolism

      Volume: 107 Issue: 4 Pages: e1477-e1487

    • DOI

      10.1210/clinem/dgab862

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protective Role of DHEAS in Age-related Changes in Bone Mass and Fracture Risk2021

    • Author(s)
      Yokomoto-Umakoshi Maki、Umakoshi Hironobu、Iwahashi Norifusa、Matsuda Yayoi、Kaneko Hiroki、Ogata Masatoshi、Fukumoto Tazuru、Terada Eriko、Nakano Yui、Sakamoto Ryuichi、Ogawa Yoshihiro
    • Journal Title

      The Journal of Clinical Endocrinology Metabolism

      Volume: 106 Issue: 11 Pages: e4580-e4592

    • DOI

      10.1210/clinem/dgab459

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Machine Learning-Based Models for Prediction of Subtype Diagnosis of Primary 1 Aldosteronism Using Blood Test2021

    • Author(s)
      Kaneko Hiroki、Umakoshi Hironobu、Ogata Masatoshi、Wada Norio、Iwahashi Norifusa、Fukumoto Tazuru、Yokomoto-Umakoshi Maki、Nakano Yui、Matsuda Yayoi、Miyazawa Takashi、Sakamoto Ryuichi、Ogawa Yoshihiro
    • Journal Title

      Scientific Reports

      Volume: - Issue: 1 Pages: 9140-9140

    • DOI

      10.1038/s41598-021-88712-8

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of deteriorated bone quality in the development of osteoporosis in pheochromocytoma and paraganglioma2021

    • Author(s)
      Yokomoto-Umakoshi Maki、Umakoshi Hironobu、Sakamoto Ryuichi、Fukumoto Tazuru、Ogata Masatoshi、Nakano Yui、Iwahashi Norifusa、Kaneko Hiroki、Mizoguchi Noriko、Hattori Akiko、Miyazawa Takashi、Matsuda Yayoi、Kawate Hisaya、Ogawa Yoshihiro
    • Journal Title

      Bone

      Volume: 142 Pages: 115607-115607

    • DOI

      10.1016/j.bone.2020.115607

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigating the causal effect of fibroblast growth factor 23 on osteoporosis and cardiometabolic disorders: A Mendelian randomization study2021

    • Author(s)
      Yokomoto-Umakoshi Maki、Umakoshi Hironobu、Miyazawa Takashi、Ogata Masatoshi、Sakamoto Ryuichi、Ogawa Yoshihiro
    • Journal Title

      Bone

      Volume: 143 Pages: 115777-115777

    • DOI

      10.1016/j.bone.2020.115777

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unilateral primary aldosteronism as an independent risk factor for vertebral fracture2020

    • Author(s)
      Yokomoto-Umakoshi M, Sakamoto R, Umakoshi H, Matsuda Y, Nagata H, Fukumoto T, Ogata M, Ogawa Y; Q-AND-A study group
    • Journal Title

      Clin Endocrinol (Oxf)

      Volume: 92 Issue: 3 Pages: 206-213

    • DOI

      10.1111/cen.14145

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pheochromocytoma and paraganglioma: An emerging cause of secondary osteoporosis2020

    • Author(s)
      Yokomoto-Umakoshi M, Umakoshi H, Fukumoto T, Matsuda Y, Nagata H, Ogata M, Kawate H, Miyazawa T, Sakamoto R, Ogawa Y; Q-AND-A study group
    • Journal Title

      Bone

      Volume: 133 Pages: 115221-115221

    • DOI

      10.1016/j.bone.2020.115221

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coexistence of osteoporosis and atherosclerosis in pheochromocytoma: new insights into its long-term management2020

    • Author(s)
      Yokomoto-Umakoshi M.、the Q-AND-A study group、Umakoshi H.、Ogata M.、Fukumoto T.、Matsuda Y.、Miyazawa T.、Sakamoto R.、Ogawa Y.
    • Journal Title

      Osteoporosis International

      Volume: 31 Issue: 11 Pages: 2151-2160

    • DOI

      10.1007/s00198-020-05527-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of aldosterone gradient within left adrenal vein in diagnosing unilateral subtype of primary aldosteronism2020

    • Author(s)
      Ogata Masatoshi、Umakoshi Hironobu、Fukumoto Tazuru、Matsuda Yayoi、Yokomoto‐Umakoshi Maki、Nagata Hiromi、Wada Norio、Miyazawa Takashi、Sakamoto Ryuichi、Ogawa Yoshihiro、the Q‐AND‐A Study Group
    • Journal Title

      Clinical Endocrinology

      Volume: 94 Issue: 1 Pages: 24-33

    • DOI

      10.1111/cen.14320

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of Discordant Results Between Confirmatory Tests in Diagnosis of Primary Aldosteronism2020

    • Author(s)
      Fukumoto Tazuru、Umakoshi Hironobu、Ogata Masatoshi、Yokomoto-Umakoshi Maki、Matsuda Yayoi、Motoya Misato、Nagata Hiromi、Nakano Yui、Iwahashi Norifusa、Kaneko Hiroki、Wada Norio、Miyazawa Takashi、Sakamoto Ryuichi、Ogawa Yoshihiro
    • Journal Title

      The Journal of Clinical Endocrinology & Metabolism

      Volume: 106 Issue: 2 Pages: e866-e874

    • DOI

      10.1210/clinem/dgaa812

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 骨粗鬆症・サルコペニアにおける副腎由来ホルモンの役割2022

    • Author(s)
      馬越真希
    • Organizer
      第40回日本骨代謝学会学術集会 あり方委員会企画 シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 副腎由来ホルモンの多様性に基づいた骨粗鬆症進展機構の解明と医学応用2022

    • Author(s)
      馬越真希
    • Organizer
      第40回日本骨代謝学会学術集会 あり方委員会企画 2020年度研究助成成果報告
    • Related Report
      2022 Annual Research Report
    • Invited

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Published: 2020-04-28   Modified: 2024-01-30  

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